Robert Holmgren Professor; Director, Program in Biological Sciences

Research Summary:

Our laboratory studies Hedgehog signal transduction, which plays a central role in animal development and human disease.  The lab is focused on several areas: the identification and characterization of new pathway components, functional studies of the pathway, the analysis of non-canonical Hedgehog signaling in metabolism, and in collaboration with the Meade lab, the development of compounds to block Hedgehog signaling in cancer.  

Selected Publications:

Functional Disruption of Gli1-DNA Recognition via a Cobalt(III) Complex. Brue CR, Dukes MW, Masotti M, Holmgren R.A, Meade TJ. ChemMedChem. 2022 Apr 20;17(8):e202200025. doi: 10.1002/cmdc.202200025.

Engrailed, Suppressor of fused and Roadkill modulate the Drosophila GLI transcription factor Cubitus interruptus at multiple levels. Roberto N, Becam I, Plessis A, Holmgren R.A. Development. 2022 Mar 15;149(6):dev200159. doi: 10.1242/dev.200159.

Delivery of Targeted Co(III)-DNA Inhibitors of Gli Proteins to Disrupt Hedgehog Signaling. Dukes MW, Bajema EA, Whittemore TJ, Holmgren R.A., Meade TJ. Bioconjug Chem. 2022 Apr 20;33(4):643-653. doi: 10.1021/acs.bioconjchem.2c00063.

Regulation of the RNA-binding protein Smaug by the GPCR Smoothened via the kinase Fused. Bruzzone L, Argüelles C, Sanial M, Miled S, Alvisi G, Gonçalves-Antunes M, Qasrawi F, Holmgren R.A., Smibert CA, Lipshitz HD, Boccaccio GL, Plessis A, Bécam I. EMBO Rep. 2020 Jul 3;21(7):e48425. doi: 10.15252/embr.201948425.

Dose-dependent transduction of Hedgehog relies on phosphorylation-based feedback between the G-protein-coupled receptor Smoothened and the kinase Fused. Sanial M, Bécam I, Hofmann L, Behague J, Argüelles C, Gourhand V, Bruzzone L, Holmgren R.A., Plessis A. Development. 2017 May 15;144(10):1841-1850. 

Control of the dynamics and homeostasis of the Drosophila Hedgehog receptor Patched by two C2-WW-HECT-E3 Ubiquitin ligases. Brigui A, Hofmann L, Argüelles C, Sanial M, Holmgren R.A., Plessis A. Open Biology. 2015; 5(10):150112. 

Chemical map of Schizosaccharomyces pombe reveals species-specific features in nucleosome positioning. Moyle-Heyrman G, Zaichuk T, Xi L, Zhang Q, Uhlenbeck OC, Holmgren R.A., Widom J, Wang JP. Proc Natl Acad Sci USA. 2013 Dec 10; 110(50):20158-63. 

Specific Inhibition of the Transcription Factor Ci by a Cobalt(III) Schiff Base-DNA Conjugate. Hurtado RR, Harney AS, Heffern MC, Holbrook RJ, Holmgren R.A., and Meade TJ. Molecular Pharmaceutics. 2012 February 6;9(2):325-333.